O, o-dimethyl-o-(3-methyl-4-nitrophenyl) thionophosphate



United States Patent:

CHaO S Further, the present invention relates to the method for manufacturing the above mentioned compound comprising condensing 0,0-dimethyl chlorothionophosphate and a compound selected from the group consisting of 3- methyl-4-nitrophenol and its alkali metal salts. The said new ester is useful for killing agricultural injurious insects, especially borers of rice, for example, rice stem borer (Chilo suppressalis Walker), paddy borer (Schoenobius incertellus Walker), purplish stem borer (Sesamia inferens Walker), and others (such as Chilo plejadellus Zinck, Chilotrea polychrysa Meyr., Scirpophaga albinella Cramer, Scz'rpopagha innotata Walker, Eldana dichromellus Walker, and Elasmopalpus lz'gnosellus Zeller), and sanitary injurious insects, especially house fly (Musca domestica Linne), and its larva, and the like.

Accordingly, an object of the present invention is to provide a new organophosphoric acid ester which is very useful as an essential active ingredient of pesticidal composition and further has a characteristic of low order of toxicity.

This application is a division of Serial No. 50,573, filed August 19, 1960, now Patent No. 3,091,565.

It has been well known that organo-phosphoric acid esters having 4-nitrophenyl radical therein possess a high degree of insecticidal activity and consequently are very useful as the active ingredient of agricultural chemicals. However, they have, at the same time, a very high degree of toxicity towards warm blooded animals and this is, indeed, the weak point of those compounds. Therefore, many attempts have been made to embody a compound having lower toxicity and higher insecticidal activity by the American and the German researchers and compounds such as Chlorthion (Farbenfabriken Bayer A.G.) and Dicapthon (American Cynamid Co.) have been found as the results of their efforts. However, these so-called low toxic insecticidal compounds have really a certain degree of low toxicity but at the same time they cannot help being inferior to some extents in their insecticidal activities.

The present inventors have made various studies for the purpose of obtaining the compound which had a low toxicity and also a high degree of insecticidal activity, such compound being anxiously desired in rice producing districts. As the result, the inventors have succeeded in obtaining the present compound which has not only extremely low toxicity but also the superior activity towards insects, compared with that of any conventional insecticidal compounds. Concretely speaking, such compounds as parathion, methyl parathion, EPN (Du Pont 3,135,780 Patented June 2, 1964 ice de Nemours, E. 1., and Co.) and Dipterex (Farbenfabrikcn Bayer A.G.) have been utilized these days as a killing agent for borers of rice. However, even though the preceding three compounds indeed possess superior insecticidal activities towards borers of rice, they have, at the same time, a high degree of toxicities toward warm blooded animals, for example, the LD value for mouse oral toxicity, of parathion being 6-10 mg./kg. of body weight, and therefore, close attention and careful management should be paid for the handling of the insecticidal compositions containing these compounds. On the other hand, it is true that Dipterex has a considerably lower toxicity towards warm blooded animals, but the insecticidal activity of the compound is inferior in proportion to that of the aforesaid three compounds. Roughly speaking, about twice or thrice as much amount as the former compounds would be necessary to attain the same degree of control of borers of rice with the latter compound. Such a larger quantity would not be tolerable from an economical point of view. Consequently, in spite of extreme toxicity towards warm blooded animals, parathion preparations have commonly been utilized as the killing agent for borers of rice up to this time. However, the present compound of the invention, has, as minutely described hereinafter, about times lower toxic effect than that of parathion and about several times lower than that of Dipterex (for example, oral toxicity towards mouse, LD value, is 700-900 mg./kg. of body weight), so it may be said that the compound is substantially non-toxic. Moreover, as minutely described hereinafter with numerical values, the efiicacy of the compound to borers of rice is not at all inferior to parathion, therefore it may fairly be said that the controlling problem of borers of rice comes to a perfect solution in fact by the appearance of the present invention.

0,0 dimethyl 0 (3-methyl-4-nitrophenyl) thionophosphate of the present invention is a new compound unknown in any preceding literature. In order to produce the compound according to the method of the invention, as shown in the following scheme of reaction,

CH; (EH30 S P MO N02 OH O G1 (I) (II) (wherein M stands for hydrogen or an alkali metal atom), 0,0-dimethyl chlorothionophosphate (I) is condensed with a compound selected from the group consisting of 3-methyl-4-nitrophenol and its alkali metal salts (II).

0,0-dimethyl chlorothionophosphate utilized in the present process as a raw material is the known liquid compound and possesses the characteristic of B.P. 66 C./ 16 mm. Hg. 3-methyl-4-nitrophenol utilized as another raw material is also prepared by any known method, for example by the method disclosed in I Chem. Soc., 1924, 125, 307, and the compound may easily be converted to the salts by reacting the phenol with a compound such as caustic alkali, alkali carbonate, alkali metals and alkali metal alcoholates in water or an organic solvent. As for the said alkali, sodium or potassium is preferable.

In the method of this invention, the condensation reaction of these raw materials may successfully be carried out by mixing the two reactants at the ratio of at least equal molecular weights, or if possible, with excess of 0,0-dimethyl chlorothionophosphate. In this case, it is preferable to carry out the reaction in an inert organic solvent by use of almost equimolar quantities of the said two compound in general. That is, when 0,0-dimcthyl chlorothionophosphate is mixed with alkali metal 3- methyl-4-nitrophenolate in an inert organic solvent and then heated, at dealkali metal chloride reaction takes place and the compound of this invention can be produced as the result. When free 3 -methyl-4-nitrophenol is utilized in place of the said alkali metal 3-methyl-4- nitrophenolate, the present reaction proceeds according to the so-called de-hydrogen chloride reaction, and in such case, the said reaction may preferably be carried out in the presence of a well known deacidic agent, for example, such organic bases as pyridine and diethyl amine, alkali metal carbonates and alkali metal bicarbonates. The inert organic solvent utilized in the present reaction may include any kind of well known solvent, provided that it does not aifect the present reaction, for example hydrocarbon solvents, halogenated hydrocarbon solvents, alcohols, ketones and ethers. Though the present reaction may proceed only by standing the reaction mixture at the room temperature for long periods of time, it is in general preferable to heat the mixture, for example at a certain temperature lower than the boiling point of the said solvent. Furthermore, the present reaction is preferably carried out in the presence of catalyst such as copper powder and cuprous salts, in good yield.

When the reaction is over, the precipitated alkali metal chloride or hydrochloric acid salt of organic base is filtered off, or alternatively, adequate quantities of water are added to the reaction mixture to dissolve the byproduced salts and water layer is separated off, and then the organic layer is evaporated in vacuo to obtain the objective compound as a residue. By the above-mentioned procedure, a sufiiciently purified compound for most practical uses may be obtained, but, if necessary, thus obtained compound may be further purified by vacuum distillation and/or column-chromatography. Generally, as the present compound is accompanied with some extents of decomposition in heating, it may be practical to use without such purification.

Thus obtained 0,0 dimethyl O (3 methyl-4-nitrophenyl) thionophosphate of the present invention is a pale yellow oily product having such physical properties as a refractive index n 1.5498 and BF. 140-145 C./0.l mm. Hg (accompanying decomposition), and this compound is very soluble in alcohols, ethers, ketones and aromatic hydrocarbons, hardly soluble in aliphatic hydrocarbons and insoluble in water.

The following is the description on the toxicity of 0,0-dimethyl O (3-methyl-4-nitrophenyl) thionophosphate of this invention. The toxicity (LD value) towards mouse of the present compound is compared with that of parathion varying their administration routes and the results are shown in Table 1.

TABLE 1 Compound or the invcntion, mgJkg.

Parathion,

Route mgJkg.

Oral administration Subcutaneous administration- Intraperitoneal administration- Dermal application Further, an outstanding characteristic of low toxicity of the present compound will be apparent from the following Table 3. In the Table 3, the toxic values towards mouse and the relative efiicacies towards rice stem borer (Clzilo suppressalis Walker) of the compound of the present invention and of the known, practically utilized insecticides are shown.

TABLE 3 Oral tox- Relative icity toeflicaey Compound wards towards (name) mouse rice stern LDsu borcr mg./kg.

P C lI O O -NOz 6-10 (parathion) (EH 0 S P C1130 O N 01 20-30 100 (methyl parathion) I O NO 1 -2 9o cinao 2 5 O (EIN) CII O O P (EH30 (EH-C 013 300-400 50 (Dipterex) CHKO S 01 CHaO O NO: 300-350 25 (Chlortllion) CHsO S I CIIaO o-N0, 300-350 50 (Dicapthon) CH O S P I 01130 0 NO: 700-900 100 (compound of the invention) The relative etficacy towards rice stem borer was detor-ruined by the so-ealled pot test by spraying the test medium on the second generated larvae of the insect and each value was set forth by comparing the efiicacy of the test compound towards rice stem borer with that of parathion (:100). The pot test was conducted in the following manner. The rice plants, 4550 days after planting thereof, were transplanted into a porcelain pot (whose surface area was 1/5000 are) and at the end of 60-70 days thereafter, rice stem borer eggs were applied to the plants. The thus heated pots were settled in a hatching room. After 4 days from the batching of the insects, each pot was sprayed with an emulsion of the test compound made by dilution of 50% emulsitiable concentrate composition (comprised of 50 parts active ingredient, 35 parts Triton X-100 (a polyethylene glycol nonylphenylether, made by Rohm & Haas Co., U.S.A.) and 15 parts xylene, by weight) with water.

By changing the concentration of the solution to be employed, the numerical values necessary for killing 85% of the insects were determined and the comparative efficacy was calculated for each compound. These tests were repeated 5 times with each compound and their mean values were calculated.

6 0,0-dimethyl-O-(3-methyl-4-nitrophenyl) th onopho phate of the present invention occupies a unique position among other isomers, homologues and analogues of the compound as regards correlation of the toxicity and the insecticidal activity, and these facts are shown in the following Table 4.

TABLE 4 Oral Hibernating larvae of Azuki toxicity rice stem borer, topiboan towards cal method 1 weevils, Compound mouse, dipping,

LDgn L050 (mg/kg.) 207/ 6.77/ 27/ 0.67'7/ (1 .9.11)" larra larva larva larva CHaO S P l CHQO O NO: 700-900 100 100 100 100 16. 7

(compound of the invention) CQH5O S P l CZHEO O NOz 17.5 100 100 100 60 5.2

CHaO

CH3 1 c1130 ONO2 100 100 100 100 83.0

Cal-I 0 0 CH3 C2H50/ O-NO: 7.4 100 100 100 10 66.4

\P CH5 c1130 N0r 920 so 0 0 o 20.0

CgH5O S CH: /P\ 64 0 0 0 0 300 027E150 0 -NO:

CHSO 0 OH: /I\ l 6040 20 0 0 0 77 CHaQ 0N0a (EH 0 O P 0 0 0 0 450 C2H5O O NOQ Cll'aO S P l 890 30 0 0 4,170 CHQO 0- CII:

/P\ 54 80 30 0 0 1, 540 (lg H5O 0 --CH3 C2Hs0\ /S NO See footnotes at end of table.

1 Topical test was conducted by using hibernating larvae of rice stem borer as follows. Each compound was dissolved in acetone to prepare a series of acetone solutions containing from0.067 to 2% of the said compound (g./ cc.) Each 1/1000 cc. of the said solution was applied to the body of the larva by means of micrometer syringe and, after keeping it for 3 days at 25 0., its death or survival condition was observed. The larvae utilized in this test had almost the same body weights ranging from 80 to 90 mg and each solution was applied to a group of these larvae in order to calculate the mean fatal percent.

1 The dipping test was conducted by using Azuki bean weevils as follows. That is, emulsifiable concentrate having the same composition with that of the aforesaid pot test (see Table 3) was prepared on each compound and the concentrate was diluted with water to obtain various concentrations of the test emulsions (ca. 1/lO0-1/100,000) In these emulsions, each group of 30 weevils was dipped for 1 minute and then transferred to a Petri's dish having a sheet of filter paper at the bottom.

Nonefiective.

After standing overnight at C., the dead and the survival numbers of the weevils were counted. This ex- Pot-test towards the second generated larvae of rice stem borer (spraying towards the borer encroaching in a rice periment was triplicated and LC value was calculated plant) based upon the concentration utilized and the kill percent, on each compound. 1 1000 1 2000 1 4000 The following Table 5 shows the comparative efiicacies towards rice stem borer of the tfon'lpound of the inveri 5 spmytg days later fro the encroach.

men: iron and of the typical curren y employed msecticid Compound 0mm inventlonuunn 9 ms 952 comp 1 g r dotall- Dipterex 99.4 88.7 92.1 S Pagaflhionrfnfunnti "1.1.- 99.5 87.0 86.4

pray ays aer rom e encroac TABLE 5 d fth in ti 9s 9 96 5 5 111i 8 V611 011-.---- Topical applzcatzon towards hibernating larvae of race 40 .,Z.,. 100 9&5 8 Stem b Parathion. 100 100 95.4

Sprayt8 days later from the encroach- 111911 I 207/ 27/ 0577/ 037/ Compoundoftheinvention 100 100 1W larva 1am 1am ?.i?ii;;. 3?:2 2212 1:33:33:

Compound 0mm invention 109 100 100 100 60 5 Parathion 100 100 100 50 Besides rice stem borer, the compound of the present invention also possesses an excellent efficacy towards TABLE 6 Con- Adult Mag- Spraying to generative place 4 centrafly, g fi Compound tion, kill kill gJlOO percent percent The After After After After After co. day lday 2days 3days 4days 7days Compound of the invention 0.25 99.5 99.4 89.2 85.2 91.3 73.0 Ma1athi0n. 1.00 99.5 95.0 100 78.5 59.2 43.0 35.9 manned..- 0.125 99.5 99.0 100 93.5 34.0 91.3 87.2 Dipterex. 0.5 67.6 97.4 100 97.0 51.3 25.2 3.2 DDVP.--- 0.5 99.5 94.7 98.8 85.2 18.1 3.2 Baytex 0.125 59.1 95.7 97.8 73.9 53.4 54.4 73.2 Dicapthon- 0.25 100 93.8 100 93.5 61.8 52.5 44.5 Dirnethoate 0.0312 63.9 98.2 95.5 96.3 95.5 100 98.5 Untreated-- 8. 6 3. 5 1. 7 0. 6 0. 8 2. 0 2. 3

1 The concentration, g./100 cc., shows the amounts (g.) of the active ingredient contained in 100 cc. of the test emulsion, and these values shown in t so that the kill percent of maggot came to mor 1 By means of the settling tower method.

3 By means of the Beaker method. That is, a culture ground of 9 than 90%.

(CI. Bull. Ent. Res. 14, 223 (1924)).

house fly was settled his item were adequately chosen in a dish having an inner diameter of abou sugar was added thereto and mixed well. the test emulsi generative place, 1 cc. of

t 16 cm., and a hel ght of about 8 9111., and 5 g. of To the dish, which was regarded as an artificial on was sprayed. After that, adult flies were put therein every day and their vital states were observed. This experiment is concerned with the residual effectiveness of the test compound.

7 paddy borer, purplish stem borer and other borers attacking rice plants. While the compound and the composition of the present invention show, as described hereinbefore, an outstanding practicability for the control of borers of rice compared with that of any other conventional insecticides, they further have superior efficacies towards common agricultural pests belonging to the order such as Lepidoptera, Diptera, Hemiptera, Siphonoptera, Orthoptera Coleoptera and other various sanitary pests.

In order to make clear the effectiveness of the compound of the present invention towards sanitary pests, Table 6 shows the comparative efiicacies towards house fly and its larva (maggot), of the compound and of the conventionally utilized, low toxic insecticides. In this test, an emulsifiable concentrate was prepared by mixing 50 parts by weight of an active ingredient, 30 parts by weight of Triton X-100 and 20 parts by weight of xylene, and the concentrate was diluted with water to make a test emulsion.

The following Table 7 shows the insecticidal activity of the compound of the invention towards other pests than the above described injurious insects.

(50.E. means an emulsifiable concentrate containing 50 parts by weight of the compound of the invention, 20 parts by weight of xylene, and 30 parts by weight of Triton X-100 [a polyethylene glycol nonylphenyl ether, made by Rphm 8r Haas Co.]

In order to put the 0,0-dimethyl-O-(3-methyl-4-nitrophenyl) thionophosphate of the present invention into practical use, various inert carriers may be combined therewith to make an insecticidal composition containing a toxic quantity of the said compound. As for the said compositions, such formulations as emulsion, suspension, dust and oil preparation may be included.

* The emulsified preparation of the compound of the invention may be prepared, for example, by mixing the compound with an organic solvent and a surface active agent in a proper proportion to make an emulsifiable concentrate and by diluting thus obtained concentrate with water at the time of practical use. As the organic solvent, an aromatic hydrocarbon such as benzene and xylene may preferably be utilized and as the surface active agent, almost all kinds of nonionic surface active agents may successfully be employed. The mixing ratio of these ingredients can freely be selected according to the material to be utilized and to the object of the preparation. However, in general, 50 weight parts of the compound of the present invention may adequately be combined with 20 weight parts of a solvent and 30 weight parts of a surface active agent to obtain a good emulsifiable concentrate. In some cases, the compound of the present invention may be combined merely with a nonionic surface active agent to obtain an emulsifiable concentrate. At the time of practical use, the said concentrate will be diluted with an adequate quantity of water to make emulsion and thus obtained emulsion will be sprayed directly.

In case of wettable powder, the compound of the present invention is mixed with a nonionic surface active agent in an adequate proportion and is further combined with a powdered carrier. As the surface active agent, almost all sorts of nonionic surface active agents may successfully be employed, and as the powdered carrier such carriers as talc, kaolin, bentonite, diatomsceous earth and Japanese acid clay may-be utilized; As for the said powdered carrier, it is preferable-to use such 3 ca!- rier as having more than 200 mesh particle size.

powder can preferably be determined so as to contain from 5 to 25 weight percent of the compound of the present invention, from 5 to 10 weight percent of the surface active agent and the remaining weight percent admixed with a powdered'carrier, a dust formulation may be obtained. In this case, it may be prepared by admixing the both materials directly, but preferably, the compound of the present invention may be dissolved in a.

solvent having alower boiling point, and admixed with the carrier, followed by distillation of the solvent to obtain the dust formulation. In the said dust formulation, it is preferable to contain from 1 to 5% by weight of the compound of the invention. As for thecarrier, such material as already described under the item of the wettable powder as the powdered carrier may successfully be utilized. 1

Further, the compound of the invention maybe dissolved in such a solvent as deodorized kerosene to make an oil preparation having a proper concentration. The solubility of the present compound in kerosene is rather poor so that one may use at the same time a co-solvent in case of need. As for the said co-solvent, such aromatic- EXAMPLE 1 To a mixture of 30.6 g. of 3-methyl-4-nitrophenol and 27.6 g. of anhydrous potassium carbonate in 200 cc. of methyl isobutyl ketone, 32.2 g. of 0,0-dimethyl chlorothionophosphate was added drop by drop at '60 C. under stirring. After the dropping of the phosphate is over, stirring of the mixture was further continued for 8 hours at 60-80 C. to complete the reaction. Water was added to dissolve the precipitated'inorganic compound, the organielayer was separated, washed with water and dried over anhydrous sodium sulfate. After distilling 03 the methyl isobutyl ketone in vacuo, 48.8 g. of reddish brown oil product was obtained. For'further purification, the crude product was subjected to columnchromatography using active carbon and active alumina, obtaining a pale yellow oily product having a refractive index r1 1.5498.

Analysis.-Calculated (for C H NO PS): P, 11.2; S, 11.6; N, 5.05%. Found: P, 11.3; S, 11.4; N, 5.11%.

EXAMPLE 2 To a mixture of 30.6 g. of 3-methyl-4-nitrophenol, 32.2 g. of 0,0-dimethyl chlorothionophosphate, and 0.1 'g. of cuprous chloride in ml. of toluene heated at 60" (3., there was added 27.6 g. of anhydrous potassium carbonate in small portions. The water resulting during the reaction is distilled off azeotropically with the toluene together with the resulting carbon dioxide. After completion of the reaction, the reaction product is treated by the same procedure as that of Example 1, yielding almost the same amount of the objective product.

Thc' mixing ratio of these ingredients in'the said wettsbleg 11 EXAMPLE 3 The procedure of Example 1 was repeated except that the corresponding amount of sodium 3-methyl-4-nitrophenolate was employed in place of 3-methyl-4-nitrophenol and anhydrous potassium carbonate, and that chlorobenzene was utilized as the solvent instead of the methylisobutyl ketone. The same result was obtained as that of the preceding examples.

EXAMPLE 4 Fifty parts of 0,0-din1ethyl-O-(3-methyl-4-nitrophenyl) thionophosphate was combined with 35 parts of Triton X-100 (a polyethylene glycol nonylphenyl ether, made by Rohm & Haas Co., USA.) and 15 parts of xylene in the described order to make a uniform emulsifiable concentrate. The rice plants after 20 days from their sowing were transplanted into the Wagner-pot having a surface area of 1/50,000 of 10 ares, each four plants a pot. After 2 months, these plants were infested with rice stem borers and, 3 days later from the encroachment of the pests, 10 cc. of 1/1000 diluted emulsion of the said 50% emulsifiable concentrate was sprayed per 12 pct. Almost of the borers encroaching in the stems were killed in 3 days.

We claim: 0,0 dimethyl-O-(3-methyl-4-nitrophenyl) thionophosphate.

References Cited in the file of this patent UNITED STATES PATENTS 2,520,393 Fletcher Aug. 29, 1950 2,701,259 Schrader Feb. 1, 1955 2,758,954 Tidwell Aug. 14, 1956 2,887,505 Blair May 19, 1959 2,967,884 Dunn et al. Jan. 10, 1961 FOREIGN PATENTS 814,152 Germany Sept. 20, 1951 41 Philippines Dec. 15, 1949 OTHER REFERENCES Schrader: Angew. Chem., vol. 73, pp. 331-334 (May 1961 

